PMID- 23708697
OWN - NLM
STAT- MEDLINE
DCOM- 20140227
LR  - 20191210
IS  - 1791-2431 (Electronic)
IS  - 1021-335X (Linking)
VI  - 30
IP  - 2
DP  - 2013 Aug
TI  - ERK and PI3K signaling cascades induce Nrf2 activation and regulate cell 
      viability partly through Nrf2 in human glioblastoma cells.
PG  - 715-22
LID - 10.3892/or.2013.2485 [doi]
AB  - The ERK and PI3K signaling cascades are aberrantly activated in human 
      glioblastoma cells, resulting in the dysregulation of numerous downstream 
      transcription factors. The dark side of the transcription factor, NF-E2-related 
      factor 2 (Nrf2) in human cancer has been revealed. It has been accepted that high 
      levels of Nrf2 promote tumor progression. In the present study, we investigated 
      the effect of the ERK and PI3K signaling cascades on Nrf2 in human glioblastoma 
      cells. Immunohistochemical staining for Nrf2 in clinical specimens showed that 
      the expression and nuclear localization of Nrf2 were increased in human 
      glioblastoma tissues when compared to peritumoral normal tissues. In addition, we 
      detected decreased nuclear localization of Nrf2 following combined treatment with 
      ERK and PI3K inhibitors in three human glioblastoma cell lines and selected the 
      cell line (U251) most sensitive to the inhibitors for further study. Our data 
      demonstrated that inhibition of ERK and PI3K not only suppressed the nuclear 
      accumulation of Nrf2 protein but also decreased the expression of the Nrf2 
      protein. In addition, combined inhibition of ERK and PI3K also decreased the mRNA 
      levels of Nrf2 target genes. Finally, we found that Nrf2 overexpression partly 
      reversed the ERK and PI3K inhibitor-induced inhibition of cell viability. 
      Therefore, the ERK and PI3K signaling cascades regulate the expression and 
      activation of Nrf2 and control cell viability partly through Nrf2 in U251 human 
      glioblastoma cells. Thus, targeting the ERK and PI3K signaling cascades for Nrf2 
      activation may provide new methods for the treatment of glioblastoma.
FAU - Cong, Zi-Xiang
AU  - Cong ZX
AD  - Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing 
      University, Nanjing, Jiangsu 210002, PR China.
FAU - Wang, Han-Dong
AU  - Wang HD
FAU - Wang, Jia-Wei
AU  - Wang JW
FAU - Zhou, Yuan
AU  - Zhou Y
FAU - Pan, Hao
AU  - Pan H
FAU - Zhang, Ding-Ding
AU  - Zhang DD
FAU - Zhu, Lin
AU  - Zhu L
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130523
PL  - Greece
TA  - Oncol Rep
JT  - Oncology reports
JID - 9422756
RN  - 0 (NF-E2-Related Factor 2)
RN  - 0 (NFE2L2 protein, human)
RN  - 0 (Phosphoinositide-3 Kinase Inhibitors)
RN  - 0 (RNA, Messenger)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
SB  - IM
MH  - Brain Neoplasms/enzymology/genetics/*metabolism/pathology
MH  - Cell Line, Tumor
MH  - Cell Nucleus/genetics/metabolism
MH  - Cell Survival/physiology
MH  - Extracellular Signal-Regulated MAP Kinases/antagonists & 
      inhibitors/genetics/*metabolism
MH  - Glioblastoma/enzymology/genetics/*metabolism/pathology
MH  - Humans
MH  - *MAP Kinase Signaling System
MH  - NF-E2-Related Factor 2/genetics/*metabolism
MH  - Phosphatidylinositol 3-Kinases/genetics/*metabolism
MH  - Phosphoinositide-3 Kinase Inhibitors
MH  - RNA, Messenger/genetics
MH  - Transcriptional Activation
EDAT- 2013/05/28 06:00
MHDA- 2014/02/28 06:00
CRDT- 2013/05/28 06:00
PHST- 2013/03/06 00:00 [received]
PHST- 2013/04/19 00:00 [accepted]
PHST- 2013/05/28 06:00 [entrez]
PHST- 2013/05/28 06:00 [pubmed]
PHST- 2014/02/28 06:00 [medline]
AID - 10.3892/or.2013.2485 [doi]
PST - ppublish
SO  - Oncol Rep. 2013 Aug;30(2):715-22. doi: 10.3892/or.2013.2485. Epub 2013 May 23.